The (Non) Law of Drug Shortages

The United States is currently experiencing the most severe shortages of certain drugs in its history. Maybe this is not “news” in the sense that an inability to obtain a very few types of drugs and dosage forms has been ongoing now for a few years, but in recent months the shortages have grown immensely in both breadth and depth. That is reality. The bigger question is: Why? How did it happen? Why didn’t anyone see it coming or issue warnings that clinicians had better start investigating alternatives to the drugs they could no longer obtain in the necessary and appropriate quantities?

Surprisingly enough, the answer might be as simple as that there are no significant, coherent, or substantial laws or regulations requiring manufacturers and distributors of most drug types to give notice to any federal or state authority if they decide to stop manufacturing a drug or dosage form or if bulk supplies from which the finished dosages are formulated are in short supply. If anyone has ever demanded, “There ought to be a law,” this topic cries out for one.

Scope of the Problem

At least one expert in the field claims that this is the worst shortage of drug supplies experienced in the U.S. in the last 30 years.1 Succinylcholine, used as a fast-acting muscle relaxant by anesthesiologists in certain kinds of trauma surgeries over the past 60 years, has been in short supply since late 2009. In fact, reported drug shortages are at the highest level in more than a decade, according to Erin Fox, manager of the Drug Information Service at the University of Utah, who provides comprehensive information on shortages to the American Society of Health-System Pharmacists. The service recorded 211 new drug shortages in 2010, up from 70 shortages in 2006 and 166 in 2009. In addition, there were at least 30 unresolved shortages that occurred prior to 2010.2

While these numbers do not match up exactly, in 2010 the FDA acknowledged a record 178 medication shortages. As of October 1, 2011, the FDA recognized approximately 232 drugs as not available in the necessary amounts.3,4 According to Valerie Jensen, RPh, associate director for the Drug Shortage Program in the FDA’s Center of Drug Evaluation and Research, most of the undersupplied drugs are older, sterile injectable drugs. Many are complicated to manufacture and most are sold as inexpensive generics. Making the picture even worse, only seven manufacturers produce these products. While there are multiple explanations for the shortages, going so far as to blame the Japan earthquake earlier this year for interrupting bulk drug flow, the more significant problem is that some companies have decided to stop making some of these drugs because the profit margin does not justify the expense. Ms. Jensen explained that the FDA does not have the authority to force manufacturers to increase production.5

(Non) Laws and Regulations

This is not to say that the FDA has no power of persuasion. By working with the drug companies and monitoring supplies of crucial ingredients, the FDA was able to prevent 38 different drug shortages in 2010 and at least 99 as of October 1, 2011. Unfortunately, with one vague exception, there is no organized mechanism for the FDA to obtain supply-side data from manufacturers. Reporting foreseeable shortages to the FDA is strictly voluntary. The exception is when the sole manufacturer of a product decides to discontinue production of a “life-supporting” or “life-sustaining” medication (whatever that means). But even this mandate has no enforcement consequences because there are no penalties associated with failure to make a “required” report.

WebMD reports: “Congress is considering an amendment to the Food, Drug and Cosmetic Act that would require early notification of the FDA by prescription drugmakers if they’re planning to stop making a drug. Even if there is more than one manufacturer, shortages can arise when one drops out of the market.”6 Congress has had several bills pending in both houses and has recently held hearings on the subject, but has failed to adopt any statutes that would alleviate the issues.7 Addressing this problem, the FDA published notice in the Federal Register in July 2011 of a workshop on how to best handle potential shortages.8 However, President Barack Obama issued an executive order on October 31, 2011, saying the administration cannot wait for Congress to take action.9

The order takes a multipronged approach to remedy the problem. First, “The President’s order directs FDA to broaden reporting of potential shortages of certain prescription drugs and to further expedite regulatory reviews that can help prevent or respond to shortages.” Second, “Under the President’s order, FDA will also work with to the Department of Justice, which will examine whether potential shortages have led to illegal price gouging or stockpiling of life-saving medications.” On this point, “the ranking member of the House Committee on Oversight and Government Reforms, when announcing his investigation into so-called gray markets, expressed concerns about a report that a leukemia drug whose typical contract price is about $12 per vial was being sold at $990 per vial—80 times higher. A Premier healthcare alliance report released in August estimated that the typical gray market vendor marks up prices by an averaged 650%. At the extreme, a drug used to treat high blood pressure that was normally priced at $25.90 was being sold at $1,200 due to a shortage.”10 Third, the administration:

Sent a letter to drug manufacturers reminding them of their responsibility to report the discontinuation of certain drugs to the FDA. The letter also encourages companies to voluntarily disclose to FDA potential prescription drug shortages in cases where disclosure is not currently required by law.

Increased staffing resources for the FDA’s Drug Shortage Program to address the increased workload that will result from additional early notification of potential shortages by manufacturers.

Released a report from the Department of Health and Human Services (HHS) Office of the Assistant Secretary for Planning and Evaluation that assesses the underlying factors that lead to drug shortages, as well as an FDA report on their role in monitoring, preventing, and responding to these shortages.

Beyond the Executive Order

President Obama’s executive order is designed to help alleviate drug shortages for cancer patients and others who are discovering that their drugs are not available, sometimes for months at a time. Some physicians and pharmacists say they have been able to work around some of the shortages by prescribing alternatives, but that the growing number of shortages is making that more difficult.11 HHS Secretary Kathleen Sebelius attributes part of the problem to a matter of supply and demand. “Demand for medications is growing, while capacity of manufacturing facilities has not. Now that’s not something we can control.”12 Administration officials do acknowledge, however, that it might take more than a presidential order, claiming the need for legislation to require drug makers to warn the government when a shortage might be coming.

Just to put the drug shortages in context, the phenomenon is not unique to the U.S. In November 2011, Reuters reported that “a continuing shortage of some essential medicines in Britain is to be investigated by members of parliament, following complaints by pharmacists that vital supplies are being lost to exports.”13 This report indicates that the shortages have been going on for over 2 years and have affected approximately 60% of the pharmacies in Great Britain.

Patient Care Issues

Perhaps the most significant problem with drug shortages is the effect on patient care and safety. “More than 1,000 shortage-related ‘near misses,’ errors and adverse patient outcomes, including at least two deaths and several extended hospitalizations, were reported by 1,800 respondents to a survey conducted in 2010 by the Institute for Safe Medication Practices (ISMP),” according to ISMP President Michael R. Cohen, RPh, MS, ScD. Acknowledging that this was not a scientific study, Dr. Cohen stated, “We had no idea we would see so many errors due to shortages.”14

Mistakes are most often made when substituting different medications or different formulations of the same drugs. Hydromorphone, about seven times stronger that morphine, was wrongfully administered at the morphine dosage level, resulting in two deaths. Overdoses and underdoses of epinephrine and heparin were reported due to substitution of different strength agents for standard prepared doses and preloaded syringes; the ISMP report also indicated that “one patient died and another was readmitted when the antibiotic amikacin was unavailable to treat resistant organisms.” The same report showed that use of “propofol substitutes for anesthesia resulted in phlebitis, prolonged nausea and vomiting, requiring extended hospitalization and difficulty weaning patients from breathing tubes.”15

One of the more interesting drug shortages, at least from the perspective of parents of children with attention-deficient/hyperactivity disorder (ADHD), is Adderall (dextroamphetamine/amphetamine). Increased demand and a limited supply of amphetamine have been identified as the common culprits.16 Fascinatingly enough, there is no shortage of the extended-release, brand-name form of the drug; it’s the less expensive immediate-release generic version that is all but unavailable in many parts of the country.

There is also a slightly different regulatory issue unrelated to the FDA when controlled substances are involved. The Drug Enforcement Administration (DEA) has a quota system in place that tells manufacturers of certain controlled substances how much of the drug can be produced in any given year.17 Once the quota is met, the manufacturer must stop making the drug until or unless the FDA approves production of additional quantities. It appears that the quota for the 30-mg capsules was reached sometime in October 2011, leading prescribers and parents to search for alternatives for the rest of the year. Dexedrine and Ritalin seem to be the alternatives of choice, but many psychiatrists do not believe these options are as effective.

Available Information

The FDA maintains a Web site of drug shortages,18 but it must be understood that the drugs listed on this site are based on information voluntarily supplied by manufacturers and cannot be considered complete or totally accurate. Manufacturers are encouraged to submit information to the FDA by contacting
drugshortages@fda.hhs.gov. Health care professionals and patients may also notify the FDA of shortages.

ACKNOWLEDGEMENT: The author would like to acknowledge Wayne State University doctor of pharmacy candidate Karen Munro for providing some of the research and topics contained in this article in completion of requirements for the course Pharmacy Ethics and Professional Responsibility.

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